U.S. patent number 10,074,526 [Application Number 15/367,481] was granted by the patent office on 2018-09-11 for systems and methods for rapidly screening samples by mass spectrometry.
This patent grant is currently assigned to DH Technologies Development Pte. Ltd.. The grantee listed for this patent is DH Technologies Development Pte. Ltd.. Invention is credited to Ronald F. Bonner, Stephen A. Tate.
United States Patent |
10,074,526 |
Bonner , et al. |
September 11, 2018 |
Systems and methods for rapidly screening samples by mass
spectrometry
Abstract
Systems and methods are used to rapidly screening samples. A
fast sample introduction device that is non-chromatographic is
instructed to supply each sample of a plurality samples to a tandem
mass spectrometer using a processor. The fast sample introduction
device can include a flow injection analysis device, an ion
mobility analysis device, or a rapid sample cleanup device. The
tandem mass spectrometer is instructed to perform fragmentation
scans at two or more mass selection windows across a mass range of
each sample of the plurality of samples using the processor. The
two or more mass selection windows across the mass range can have
fixed or variable window widths. The tandem mass spectrometer can
be instructed to obtain a mass spectrum of the mass range before
instructing the tandem mass spectrometer to perform the
fragmentation scans.
Inventors: |
Bonner; Ronald F. (Newmarket,
CA), Tate; Stephen A. (Barrie, CA) |
Applicant: |
Name |
City |
State |
Country |
Type |
DH Technologies Development Pte. Ltd. |
Singapore |
N/A |
SG |
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Assignee: |
DH Technologies Development Pte.
Ltd. (Singapore, SG)
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Family
ID: |
45688183 |
Appl.
No.: |
15/367,481 |
Filed: |
December 2, 2016 |
Prior Publication Data
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Document
Identifier |
Publication Date |
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US 20170084436 A1 |
Mar 23, 2017 |
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Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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14944467 |
Nov 18, 2015 |
9543134 |
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13876349 |
Feb 23, 2016 |
9269553 |
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PCT/IB2011/002594 |
Nov 2, 2011 |
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61411028 |
Nov 8, 2010 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
H01J
49/04 (20130101); H01J 49/0027 (20130101); H01J
49/0031 (20130101); H01J 49/0045 (20130101) |
Current International
Class: |
H01J
49/04 (20060101); H01J 49/00 (20060101) |
Field of
Search: |
;250/282 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Johnston; Phillip A
Attorney, Agent or Firm: Kasha; John R. Kasha; Kelly L.
Kasha Law LLC
Parent Case Text
CROSS-REFERENCE TO RELATED APPLICATION
This application is a continuation of U.S. patent application Ser.
No. 14/944,467, filed Nov. 18, 2015, which is a continuation of
U.S. patent application Ser. No. 13/876,349, filed Mar. 27, 2013,
filed as Application No. PCT/IB2011/002594 on Nov. 2, 2011, now
U.S. Pat. No. 9,269,553, which claims the benefit of U.S.
Provisional Patent Application No. 61/411,028, filed Nov. 8, 2010,
the disclosures of which are incorporated by reference herein in
their entireties.
Claims
What is claimed is:
1. A system for rapidly screening samples, comprising: a tandem
mass spectrometer that includes a quadrupole mass filter that
allows independent control of both the radio frequency (RF)
voltages and direct current (DC) voltages; a fast sample
introduction device that is non-chromatographic and that supplies
the tandem mass spectrometer with each sample of a plurality of
samples; and a processor in communication with the tandem mass
spectrometer and the fast sample introduction device that instructs
the tandem mass spectrometer to perform a survey scan of the each
sample supplied by the fast sample introduction device to obtain a
precursor mass spectrum, determines a mass distribution of
precursor ions in the each sample from the precursor mass spectrum
to define two or more adjacent wide precursor mass selection
windows across an entire mass range of interest of the each sample,
wherein at least two of the two or more adjacent wide precursor
mass selection windows have different window widths, and instructs
the tandem mass spectrometer to perform fragmentation scans at the
two or more adjacent wide precursor mass selection windows across
the entire mass range of interest of the each sample by
independently controlling the RF voltages and DC voltages of the
quadrupole mass filter of the tandem mass spectrometer.
2. The system of claim 1, wherein the fast sample introduction
device comprises a flow injection analysis device, an ion mobility
analysis device, or a rapid sample cleanup device.
3. The system of claim 1, wherein the processor instructs the
tandem mass spectrometer to vary at least one parameter of the
tandem mass spectrometer between at least two of the two or more
adjacent wide precursor mass selection windows.
4. The system of claim 1, wherein the processor instructs the fast
sample introduction device to supply the each sample to the tandem
mass spectrometer before the processor instructs the tandem mass
spectrometer to perform the survey scan of the each sample to
obtain a precursor mass spectrum.
5. The system of claim 1, wherein the plurality of samples are
injected by the fast sample introduction device.
6. A method for rapidly screening samples, comprising: instructing
a fast sample introduction device that is non-chromatographic to
supply each sample of a plurality samples to a tandem mass
spectrometer using a processor, wherein the tandem mass
spectrometer includes a quadrupole mass filter that allows
independent control of both the radio frequency (RF) voltages and
direct current (DC) voltages; instructing the tandem mass
spectrometer to perform a survey scan of the each sample supplied
by the fast sample introduction device to obtain a precursor mass
spectrum using the processor; determining a mass distribution of
precursor ions in the each sample from the precursor mass spectrum
to define two or more adjacent wide precursor mass selection
windows across an entire mass range of interest of the each sample
using the processor, wherein at least two of the two or more
adjacent wide precursor mass selection windows have different
window widths; and instructing the tandem mass spectrometer to
perform fragmentation scans at the two or more adjacent wide
precursor mass selection windows across the entire mass range of
interest of the each sample by independently controlling the RF
voltages and DC voltages of the quadrupole mass filter of the
tandem mass spectrometer using the processor.
7. The method of claim 6, further comprising instructing the tandem
mass spectrometer to vary at least one parameter of the tandem mass
spectrometer between at least two of the two or more adjacent wide
precursor mass selection windows using the processor.
8. The method of claim 6, wherein the plurality of samples are
injected by the fast sample introduction device.
9. A computer program product, comprising a non-transitory and
tangible computer-readable storage medium whose contents include a
program with instructions being executed on a processor so as to
perform a method for rapidly screening samples, the method
comprising: providing a system, wherein the system comprises one or
more distinct software modules, and wherein the distinct software
modules comprise a fast sample introduction module and a tandem
mass spectrometry module, wherein the tandem mass spectrometer
includes a quadrupole mass filter that allows independent control
of both the radio frequency (RF) voltages and direct current (DC)
voltages; instructing a fast sample introduction device that is
non-chromatographic to supply each sample of a plurality samples to
a tandem mass spectrometer using the fast sample introduction
module; instructing the tandem mass spectrometer to perform a
survey scan of the each sample supplied by the fast sample
introduction device to obtain a precursor mass spectrum using the
tandem mass spectrometry module; determining a mass distribution of
precursor ions in the each sample from the precursor mass spectrum
to define two or more adjacent wide precursor mass selection
windows across an entire mass range of interest of the each sample
using the tandem mass spectrometry module, wherein at least two of
the two or more adjacent wide precursor mass selection windows have
different window widths, and instructing the tandem mass
spectrometer to perform fragmentation scans at the two or more
adjacent wide precursor mass selection windows across the entire
mass range of interest of the each sample by independently
controlling the RF voltages and DC voltages of the quadrupole mass
filter of the tandem mass spectrometer using the tandem mass
spectrometry module.
10. The computer program product of claim 9, wherein the plurality
of samples are injected by the fast sample introduction device.
11. The computer program product of claim 9, further comprising
instructing the tandem mass spectrometer to vary at least one
parameter of the tandem mass spectrometer between at least two of
the two or more adjacent wide precursor mass selection windows
using the tandem mass spectrometry module.
Description
INTRODUCTION
In many applications there is a need for rapid analyses, either
because there are many samples to be run or the results are
required quickly. Applications that require many samples include,
but are not limited to, drug screening, drug discovery metabolism,
network biology and biological experiments, food analyses, process
monitoring, DNA analyses for forensics, and small interfering RNA
(siRNA) screening. Applications that require results to be returned
quickly include, but are not limited to, diagnosis, drug doping,
food analyses, and therapeutic monitoring.
One method of providing rapid sample analysis couples a fast
separation technique with a traditional high resolution mass
spectrometry method. For example, samples are infused into the
system at a high sample rate. One high resolution mass spectrum is
produced for each sample. The spectra of different samples are then
compared.
Although this method can identify obvious differences in small and
large molecules between samples, very few of these difference may
be indicative of items of interest such as disease. Finally, using
this method, subtle but important differences may be lost or hidden
due to additional complications that can include, but are not
limited to, ion suppression, unresolved isomers, matrix effects, or
isobaric species.
BRIEF DESCRIPTION OF THE DRAWINGS
The skilled artisan will understand that the drawings, described
below, are for illustration purposes only. The drawings are not
intended to limit the scope of the present teachings in any
way.
FIG. 1 is a block diagram that illustrates a computer system, upon
which embodiments of the present teachings may be implemented.
FIG. 2 is a schematic diagram showing a system for rapidly
screening samples, in accordance with various embodiments.
FIG. 3 is an exemplary flowchart showing a method for rapidly
screening samples, in accordance with various embodiments.
FIG. 4 is a schematic diagram of a system that includes one or more
distinct software modules that performs a method for rapidly
screening samples, in accordance with various embodiments.
Before one or more embodiments of the present teachings are
described in detail, one skilled in the art will appreciate that
the present teachings are not limited in their application to the
details of construction, the arrangements of components, and the
arrangement of steps set forth in the following detailed
description or illustrated in the drawings. Also, it is to be
understood that the phraseology and terminology used herein is for
the purpose of description and should not be regarded as
limiting.
DESCRIPTION OF VARIOUS EMBODIMENTS
Computer-Implemented System
FIG. 1 is a block diagram that illustrates a computer system 100,
upon which embodiments of the present teachings may be implemented.
Computer system 100 includes a bus 102 or other communication
mechanism for communicating information, and a processor 104
coupled with bus 102 for processing information. Computer system
100 also includes a memory 106, which can be a random access memory
(RAM) or other dynamic storage device, coupled to bus 102 for
storing instructions to be executed by processor 104. Memory 106
also may be used for storing temporary variables or other
intermediate information during execution of instructions to be
executed by processor 104. Computer system 100 further includes a
read only memory (ROM) 108 or other static storage device coupled
to bus 102 for storing static information and instructions for
processor 104. A storage device 110, such as a magnetic disk or
optical disk, is provided and coupled to bus 102 for storing
information and instructions.
Computer system 100 may be coupled via bus 102 to a display 112,
such as a cathode ray tube (CRT) or liquid crystal display (LCD),
for displaying information to a computer user. An input device 114,
including alphanumeric and other keys, is coupled to bus 102 for
communicating information and command selections to processor 104.
Another type of user input device is cursor control 116, such as a
mouse, a trackball or cursor direction keys for communicating
direction information and command selections to processor 104 and
for controlling cursor movement on display 112. This input device
typically has two degrees of freedom in two axes, a first axis
(i.e., x) and a second axis (i.e., y), that allows the device to
specify positions in a plane.
A computer system 100 can perform the present teachings. Consistent
with certain implementations of the present teachings, results are
provided by computer system 100 in response to processor 104
executing one or more sequences of one or more instructions
contained in memory 106. Such instructions may be read into memory
106 from another computer-readable medium, such as storage device
110. Execution of the sequences of instructions contained in memory
106 causes processor 104 to perform the process described herein.
Alternatively hard-wired circuitry may be used in place of or in
combination with software instructions to implement the present
teachings. Thus implementations of the present teachings are not
limited to any specific combination of hardware circuitry and
software.
The term "computer-readable medium" as used herein refers to any
media that participates in providing instructions to processor 104
for execution. Such a medium may take many forms, including but not
limited to, non-volatile media, volatile media, and transmission
media. Non-volatile media includes, for example, optical or
magnetic disks, such as storage device 110. Volatile media includes
dynamic memory, such as memory 106. Transmission media includes
coaxial cables, copper wire, and fiber optics, including the wires
that comprise bus 102.
Common forms of computer-readable media include, for example, a
floppy disk, a flexible disk, hard disk, magnetic tape, or any
other magnetic medium, a CD-ROM, digital video disc (DVD), a
Blu-ray Disc, any other optical medium, a thumb drive, a memory
card, a RAM, PROM, and EPROM, a FLASH-EPROM, any other memory chip
or cartridge, or any other tangible medium from which a computer
can read.
Various forms of computer readable media may be involved in
carrying one or more sequences of one or more instructions to
processor 104 for execution. For example, the instructions may
initially be carried on the magnetic disk of a remote computer. The
remote computer can load the instructions into its dynamic memory
and send the instructions over a telephone line using a modem. A
modem local to computer system 100 can receive the data on the
telephone line and use an infra-red transmitter to convert the data
to an infra-red signal. An infra-red detector coupled to bus 102
can receive the data carried in the infra-red signal and place the
data on bus 102. Bus 102 carries the data to memory 106, from which
processor 104 retrieves and executes the instructions. The
instructions received by memory 106 may optionally be stored on
storage device 110 either before or after execution by processor
104.
In accordance with various embodiments, instructions configured to
be executed by a processor to perform a method are stored on a
computer-readable medium. The computer-readable medium can be a
device that stores digital information. For example, a
computer-readable medium includes a compact disc read-only memory
(CD-ROM) as is known in the art for storing software. The
computer-readable medium is accessed by a processor suitable for
executing instructions configured to be executed.
The following descriptions of various implementations of the
present teachings have been presented for purposes of illustration
and description. It is not exhaustive and does not limit the
present teachings to the precise form disclosed. Modifications and
variations are possible in light of the above teachings or may be
acquired from practicing of the present teachings. Additionally,
the described implementation includes software but the present
teachings may be implemented as a combination of hardware and
software or in hardware alone. The present teachings may be
implemented with both object-oriented and non-object-oriented
programming systems.
Systems and Methods of Data Processing
As described above, rapid sample analysis is useful in increasing
sample throughput or in producing required results quickly.
Traditional methods of providing rapid sample analysis have
included coupling a fast separation technique with high resolution
mass spectrometry (MS). Such methods are often unable to reveal
complexities in the results caused by complications that can
include, but are not limited to, ion suppression, unresolved
isomers, matrix effects, or isobaric species. Another traditional
method is to use a fast separation technique to introduce the
sample, rapidly generate a MS scan and then perform tandem mass
spectrometry, or mass spectrometry/mass spectrometry (MS/MS), on
selected ions identified in the MS spectrum. In order to maintain
high throughput only a limited number of MS/MS spectra can be
acquired in this way.
In various embodiments, a fast sample introduction technique that
is non-chromatographic is coupled with a tandem mass spectrometry
technique that performs fragmentation scans at two or more mass
selection windows across an entire mass range of interest to
provide a rapid sample analysis method. This method can provide
enough MS/MS information to produce meaningful results and can
reveal important complexities in the results.
A fast sample introduction technique that is non-chromatographic
can include, but is not limited to, flow injection analysis (FIA),
mobility analysis, or a rapid sample cleanup technique. A rapid
sample cleanup technique can include, for example, a trap and elute
technique. A fast sample introduction technique can inject samples
for tandem mass spectrometry analysis at a rate or frequency of
approximately one sample per minute, for example.
Tandem mass spectrometry is used to reveal complexities in the data
between different samples. For example, tandem mass spectrometry
can resolve isomers. Nothing in a single mass spectrum reveals that
isomers of the same mass are present. However, fragmenting those
isomers can reveal that there are differences between samples at
different masses, because the fragments from a mass in one sample
can be slightly different from the fragments from the same mass in
another sample.
The specificity of a method performed on a tandem mass spectrometer
is improved by providing the mass analyzer with a narrow mass
selection window width, or precursor mass selection window width. A
narrow mass selection window width is on the order of 1 atomic mass
unit (amu), for example. Alternatively, the sensitivity of the
method is improved by providing the mass analyzer with a wide mass
selection window width. A wide mass selection window width is on
the order of 20 or 200 amu, for example.
In various embodiments, a mass selection window width with
sufficient sensitivity is selected for the first mass analysis
stage of a tandem mass spectrometer in a rapid sample analysis
method. Moving this mass selection window width allows an entire
mass range to be fragmented within a short period of time and
without the need to determine which masses to fragment.
Selecting a wider mass selection window requires fewer
fragmentation scans to cover a mass range. For example, a mass
range from 200 amu to 600 that is scanned using a narrow mass
selection window width of 1 amu requires 400 fragmentation scans.
Using a wider mass selection window width of 100 amu requires just
4 fragmentation scans. A wider mass selection window is, therefore,
used to fragment samples across the entire mass range of interest
in order to analyze samples at the rate samples are injected by the
fast sample introduction technique.
As described above, selecting a wider mass selection window
provides greater sensitivity and less specificity than selecting a
narrower mass selection for the first stage of tandem mass
spectrometry. However, any loss in specificity can be regained
through high resolution detection in the second stage of tandem
mass spectrometry. As a result, both high specificity and high
sensitivity can be provided by the overall method.
In various embodiments, fragmentation scans occur at uniform or
fixed mass selection windows across a mass range. The mass range
can include, for example, a preferred mass range of the sample or
the entire mass range of the sample.
Recent developments in mass spectrometry hardware have allowed the
mass selection window width of a tandem mass spectrometer to be
varied or set to any value instead of a single value across a mass
range. For example, independent control of both the radio frequency
(RF) and direct current (DC) voltages applied to a quadrupole mass
filter or analyzer can allow the selection of variable mass
selection window widths. Any type of tandem mass spectrometer can
allow the selection of variable mass selection window widths. A
tandem mass spectrometer can include one or more physical mass
analyzers that perform two or more mass analyses. A mass analyzer
of a tandem mass spectrometer can include, but is not limited to, a
time-of-flight (TOF), quadrupole, an ion trap, a linear ion trap,
an orbitrap, or a Fourier transform mass spectrometer.
In various embodiments, fragmentation scans occur with variable
mass selection windows across a mass range. Varying the value of
the mass selection window width across a mass range of an analysis
can improve both the specificity, sensitivity, and speed of the
analysis. For example, in areas of the mass range where compounds
are known to exist, a narrow mass selection window width is used.
This enhances the specificity of the known compounds. In areas of
the mass range where no compounds are known to exist, a wide mass
selection window width is used. This allows unknown compounds to be
found, thereby improving the sensitivity of the analysis. The
combination of wide and narrow ranges allows a scan to be completed
faster than using fixed narrow windows.
Also, by using narrow mass selection window widths in certain areas
of the mass range, other mass peaks in a mass spectrum are less
likely to affect the analysis of the mass peaks of interest. Some
of the effects that can be caused by other mass peaks can include,
but are not limited to, saturation, ion suppression, or space
charge effects.
In various embodiments, the value of the mass selection window
width chosen for a portion of the mass range is based on
information known about the samples. In other words, the value of
the mass selection window width is adjusted across the mass range
based on the known or expected complexities of the samples. So,
where the samples are more complex or have a large number of ions,
narrower mass selection window widths are used, and where the
samples are less complex or have a sparse number of ions, wider
mass selection window widths are used. The complexity of the
samples can be determined by creating a compound molecular weight
profile of the samples, for example.
A compound molecular weight profile of the samples can be created
in a number of ways. In addition, the compound molecular weight
profile of the samples can be created before data acquisition or
during data acquisition. Further, the compound molecular weight
profile of the samples can be created in real-time during data
acquisition.
In various embodiments, the compound molecular weight profile used
to define variable window widths across a mass range is preferably
created before data acquisition and used for all samples analyzed
with a rapid sample analysis method. Not varying the variable
window widths between samples allows differences between samples to
be more easily found.
Other parameters of a tandem mass spectrometer are dependent on the
mass selection window widths that are selected across a mass range.
These other parameters can include ion optical elements, such as
collision energy, or non-ion optical elements, such as accumulation
time, for example.
As a result, in various embodiments, the analysis of samples can
further include varying one or more parameters of the tandem mass
spectrometer other than the mass selection window width across a
mass range. Varying such parameters can reduce the unwanted effects
of the additional complications described above. For example,
through the fragmentation of windowed regions that do not appear to
have a precursor ion present, and by varying the accumulation time
for these windows, the potential effects of matrix suppression can
be mitigated to some extent.
In various embodiments, one or more samples can be analyzed before
the subsequent analysis that uses fixed or variable mass selection
window widths. This analysis of the samples can include a complete
analysis or a single scan. A complete analysis includes, for
example, two or more scans. A scan can be, but is not limited to, a
survey scan, a neutral loss scan, or a precursor scan. A scan can
provide, for example, a high resolution mass spectrometry (HRMS)
spectrum. An HRMS spectrum can be used to determine the accurate
mass of precursor ions, or to determine the mass distribution of
precursor ions in the one or more samples to define the window
widths, for example.
An HRMS spectrum can be used as a fingerprint of a sample. In some
cases, comparing fingerprints may already indicate differences that
would be the targets of a method of fragmenting all precursor ions
in windows across a mass range, while in others the fingerprint can
be used to determine the window widths and accumulation times. This
could be based on the peak density (areas with more peaks get
narrower windows) or the peak intensity (large peaks get narrow
windows and short accumulation times while other areas get longer
times with windows based on peak density), for example.
After a rapid sample analysis method, data is mined for information
of interest and stored for comparison with other samples or for
re-analysis, for example. Data mining is extremely fast allowing
many samples to be run, for example for network biology experiments
or high throughput screening (HTS), or to provide rapid turnaround
of the results. The information content of an assay is also very
high allowing two-dimensional (2D) maps to be generated from a
sample. Data mining tools and techniques can include, but are not
limited to, (1) libraries of expected compounds which can be used
to perform library searches and to generate ion traces or ion
profiles, (2) extraction techniques which would allow the isolation
of masses determined by the potential neutral losses which can be
seen, and (3) the use of image manipulation or other techniques for
the identification of similarities and differences in samples.
Additional levels of information can also be extracted from a rapid
sample analysis method. For example, in many cases it is possible
to perform several scans at different collision energies so that
there is additional information for identification (the breakdown
curves of the compounds) or deconvolution. For example, the MS/MS
spectra of compounds can be found by correlation across multiple
samples, i.e., the fragments that have the same behavior across
many samples are probably from the same compound. Deconvolution
involves deconvoluting the spectra of compounds by correlation.
Sample preparation is another important aspect of a rapid sample
analysis method. Sample preparation, especially fractionation, is
needed to separate compound classes, so the appropriate windows and
analytical conditions can be applied. Pre-concentration of a sample
is also potentially required, for example via solid phase
extraction, so concentrations can be increased to detectable
levels. The amount of sample preparation needed is dependent on the
sample complexity and the required sensitivity and compound
coverage. In some applications, it is minimal and in others very
extensive. However, sample preparation can be performed in an
off-line and automated manner so that actual analysis speed is
maintained.
In various embodiments, a rapid sample analysis method can
significantly enable network biology by allowing thousands of
samples to be analyzed in a reasonable time scale. Large scale
automated sample preparation is used to fractionate the sample
(perhaps 1 mL of serum or plasma) into compound classes (small
polar molecules such as sugars, nucleosides, amino acids, organic
acids; lipids; peptides; proteins; miRNA . . . ) prior to analysis.
A similar approach is used for characterizing commercial products
(small and large therapeutics, e.g.), foods, etc.
Tandem Mass Spectrometry System
FIG. 2 is a schematic diagram showing a system 200 for rapidly
screening samples, in accordance with various embodiments. System
200 includes tandem mass spectrometer 210, processor 220, and fast
sample introduction device 230. Processor 220 can be, but is not
limited to, a computer, microprocessor, or any device capable of
sending and receiving control signals and data to and from mass
spectrometer 210 and fast sample introduction device 230 and
processing data.
Tandem mass spectrometer 210 can include can include one or more
physical mass analyzers that perform two or more mass analyses. A
mass analyzer of a tandem mass spectrometer can include, but is not
limited to, a time-of-flight (TOF), quadrupole, an ion trap, a
linear ion trap, an orbitrap, or a Fourier transform mass analyzer.
Tandem mass spectrometer 210 can include separate mass spectrometry
stages or steps in space or time, respectively.
Fast sample introduction device 230 can perform a fast sample
introduction technique that is non-chromatographic and that
includes, but is not limited to, FIA, ion mobility analysis, or a
rapid sample cleanup technique. Fast sample introduction device 230
can be part of tandem mass spectrometer 210 or it can be a separate
device as shown in system 200. Fast sample introduction device 230
supplies tandem mass spectrometer 210 with each sample of a
plurality of samples.
Processor 220 is in communication with the tandem mass spectrometer
210 and fast sample introduction device 230. Processor 220
instructs fast sample introduction device 230 to supply each sample
of the plurality of samples to tandem mass spectrometer 210.
Processor 220 then instructs tandem mass spectrometer 210 to
perform fragmentation scans at two or more mass selection windows
across an entire mass range of interest of each sample. The two or
more mass selection windows are adjacent mass selection windows,
for example.
In various embodiments, the two or more mass selection windows used
across the mass range have a fixed window width. In various
embodiments, at least two of the two or more mass selection windows
used across the mass range have different window widths.
In various embodiments, processor 220 instructs tandem mass
spectrometer 210 to obtain a mass spectrum of the mass range before
processor 220 instructs the tandem mass spectrometer to perform the
fragmentation scans.
In various embodiments, processor 220 instructs tandem mass
spectrometer 210 to vary at least one parameter of tandem mass
spectrometer 210 between at least two of the two or more mass
selection windows used across the mass range.
Tandem Mass Spectrometry Method
FIG. 3 is an exemplary flowchart showing a method 300 for rapidly
screening samples, in accordance with various embodiments.
In step 310 of method 300, a fast sample introduction device that
is non-chromatographic is instructed to supply each sample of a
plurality samples to a tandem mass spectrometer using a
processor.
In step 320, the tandem mass spectrometer is instructed to perform
fragmentation scans at two or more mass selection windows across an
entire mass range of interest of each sample of the plurality of
samples using the processor.
Tandem Mass Spectrometry Computer Program Product
In various embodiments, a computer program product includes a
non-transitory and tangible computer-readable storage medium whose
contents include a program with instructions being executed on a
processor so as to perform a method for rapidly screening samples.
This method is performed by a system that includes one or more
distinct software modules.
FIG. 4 is a schematic diagram of a system 400 that includes one or
more distinct software modules that performs a method for rapidly
screening samples, in accordance with various embodiments. System
400 includes fast sample introduction module 410 and tandem mass
spectrometry module 420.
Fast sample introduction module 410 instructs a fast sample
introduction device that is non-chromatographic to supply each
sample of a plurality samples to a tandem mass spectrometer. Tandem
mass spectrometry module 420 instructs the tandem mass spectrometer
to perform fragmentation scans at two or more mass selection
windows across an entire mass range of interest of each sample of
the plurality of sample.
While the present teachings are described in conjunction with
various embodiments, it is not intended that the present teachings
be limited to such embodiments. On the contrary, the present
teachings encompass various alternatives, modifications, and
equivalents, as will be appreciated by those of skill in the
art.
Further, in describing various embodiments, the specification may
have presented a method and/or process as a particular sequence of
steps. However, to the extent that the method or process does not
rely on the particular order of steps set forth herein, the method
or process should not be limited to the particular sequence of
steps described. As one of ordinary skill in the art would
appreciate, other sequences of steps may be possible. Therefore,
the particular order of the steps set forth in the specification
should not be construed as limitations on the claims. In addition,
the claims directed to the method and/or process should not be
limited to the performance of their steps in the order written, and
one skilled in the art can readily appreciate that the sequences
may be varied and still remain within the spirit and scope of the
various embodiments.
* * * * *